Proton therapy is currently on the rise and is thus considered for treating lung cancer patients. The majority of proton therapy patients are currently being treated with passive scattered proton therapy. As newer facilities are being designed for pencil beam scanning only and existing facilities are upgrading towards beam scanning, it can be expected that beam scanning will be the method of choice in the future. Dosimetric effects of motion are potentially more severe in proton therapy than in conventional therapy due to the sharp distal dose fall-off. Furthermore, proton beam scanning can cause interplay effects between pencil beam motion and target motion. Before beam scanning can be used clinically for lung treatments it is mandatory that we understand dosimetric effects when treating moving targets with a time-dependent delivery system. This study needs to be done now, before beam scanning becomes established! Consequently, we propose to apply four-dimensional Monte Carlo to study potential interplay effects between pencil beam motion and target motion when treating moving targets with proton beam scanning. We expect that there could be under-dosage of the tumor or dose changes in organs at risk in excess of 30% depending on motion parameters and beam delivery parameters. Thus, for certain delivery and motion parameters, proton beam scanning might not be used (not even with gated delivery) instead of standard passive scattered proton beam therapy. The impact of interplay effects can be influenced by varying beam delivery parameters, e.g. pencil beam spot size, re-painting strategy, etc. We also propose to study the biological impact of scanned beam delivery with high local dose rate. PUBLIC HEALTH RELEVANCE: Proton therapy is currently on the rise and is thus considered for treating lung cancer. However, proton beam scanning can cause interplay effects between pencil beam motion and target motion. Before beam scanning can be used clinically for lung treatments it is mandatory that we understand dosimetric effects when treating moving targets with a time-dependent delivery system. This study needs to be done now, before beam scanning becomes clinically established! Consequently, we propose to apply four-dimensional Monte Carlo to study potential interplay effects between pencil beam motion and target motion when treating moving targets with proton beam scanning.